Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Joseph's disease is a hereditary ataxia found among descendants of Portuguese from the Azores Islands. We describe the clinical and pathological features of 4 members of a Japanese family who were diagnosed as having Joseph's disease. The illness began with cerebellar ataxia between the ages of 18 and 45 years. Nystagmus, dysarthria, and pyramidal signs were early manifestations. External ophthalmoplegia, dystonia and/or athetotic movements, and muscular atrophy appeared in the late stages. Neuropathological findings in one patient revealed degeneration of the dentatorubral and pallidoluysian systems, substantia nigra, pontocerebellar system, Clarke's column and spinocerebellar tracts, and anterior horn cells, as well as the cranial nuclei in the brainstem. Neurons in the inferior olivary nuclei, Purkinje's and granule cells, the cerebral cortex, thalamus, and striatum were spared. Involvement of the dentatorubral and pallidoluysian systems seems to be a characteristic feature of this disease in Japan.
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PMID:Joseph's disease: clinical and pathological studies in a Japanese family. 396 57

The patient we describe had cerebellar ataxia, slow eye movements, myoclonus, facial dystonia and signs of spinal cord and peripheral nerve involvement. The patient's mother, brother and sister died from the same disease. Neuropathological examination revealed lesions of olivo-ponto-cerebellar atrophy (OPCA) associated with spinal cord degenerative changes characteristic of Menzel's hereditary ataxia. Although myoclonus was similar to Hunt's dyssynergia cerebellaris myonica, pathological findings did not show significant involvement of the dentate nucleus or superior cerebellar peduncle and physiopathological hypotheses for myoclonus are discussed. Slow eye movement is emphasized in the propositus and we suggest that it could be specific of one type of OPCA. Its pathological significance is discussed, but a primitive and unique involvement of the paramedian pontine reticular formation is unlikely.
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PMID:Menzel's hereditary ataxia with slow eye movements and myoclonus. A clinico-pathological study. 663 53

Autosomal dominant motor system degeneration (ADMSD) is a hereditary ataxia that has been reported previously only in Portuguese families from the Azores Islands. Cerebellar ataxia, pyramidal and extrapyramidal signs, amyotrophy, dystonia, abnormal eye movements, and prominent eyes are variably present. Four members of a family had cerebellar ataxia, dystonic posturing, a variety of abnormal eye movements, and prominent eyes resulting from lid retraction. Eight other family members had a similar disease. The combination of cerebellar ataxia, dystonia, abnormal eye movements, and prominent eyes has been reported only in ADMSD. The family reported here may be the first example of ADMSD in a non-Portuguese family.
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PMID:Presumably Azorean disease in a presumably non-Portuguese family. 719 99

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia.
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PMID:Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients. 1670 60

Eighteen patients from three large multigenerational families with genetically established spinocerebellar ataxia type 2 (SCA2) were examined, with special attention to the presence of dystonic features. Cervical dystonia (CD) was diagnosed according to standardised clinical criteria. CD was scored using the Tsui score. Polymyography was performed in six cases using bilateral surface electrode recordings of the sternocleidomastoid and trapezius muscles together with needle electrode recordings of the splenius capitis muscles bilaterally. CD was found in 11 of 18 patients (61%), and was the presenting symptom in one case. Severity of CD was mild to moderate, with Tsui scores ranging from 5 to 12 points. Polymyography in 6 of 11 SCA2 patients with CD showed the typical pattern of dystonia with spontaneous, involuntary muscle activation at rest in at least one neck muscle with disturbed reciprocal inhibition of antagonistic neck muscles. CD appears to be a common clinical feature in SCA2 and may precede ataxia and gait disturbance. By contrast, none of the 18 patients had dystonic features in other body regions. CD has probably been underreported in patients with the ataxic SCA2 phenotype and should be considered as an additional clinical manifestation in patients with hereditary ataxia.
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PMID:Cervical dystonia in spinocerebellar ataxia type 2: clinical and polymyographic findings. 1722 Feb 91

Deficiency of caytaxin results in hereditary ataxia or dystonia in humans, mice and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as caytaxin-binding proteins. The tetratricopeptide-repeat region of KLC1 recognizes the ELEWED sequence (amino acids 115-120) of caytaxin. This motif is conserved among BNIP-2 family members and other KLC-interacting kinesin cargo proteins such as calsyntenins. Caytaxin associates with kinesin heavy chains (KHCs) indirectly by binding to KLCs, suggesting that caytaxin binds to the tetrameric kinesin molecule. In cultured hippocampal neurons, we found that caytaxin is distributed in both axons and dendrites in punctate patterns, and it colocalizes with microtubules and KHC. GFP-caytaxin expressed in hippocampal neurons is transported at a speed ( approximately 1 mum/second) compatible with kinesin movement. Inhibition of kinesin-1 by dominant-negative KHC decreases the accumulation of caytaxin in the growth cone. Caytaxin puncta do not coincide with vesicles containing known kinesin cargos such as APP or JIP-1. A part of caytaxin, however, colocalizes with mitochondria and suppression of caytaxin expression by RNAi redistributes mitochondria away from the distal ends of neurites. These data indicate that caytaxin binds to kinesin-1 and functions as an adaptor that mediates intracellular transport of specific cargos, one of which is the mitochondrion.
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PMID:Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains. 1986 99

Gene therapy is a potential therapeutic strategy for treating hereditary movement disorders, including hereditary ataxia, dystonia, Huntington's disease, and Parkinson's disease. Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome using modified nucleases. Recently, clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (CRISPR/Cas9) has been used as an essential tool in biotechnology. Cas9 is an RNA-guided DNA endonuclease enzyme that was originally associated with the adaptive immune system of Streptococcus pyogenes and is now being utilized as a genome editing tool to induce double strand breaks in DNA. CRISPR/Cas9 has advantages in terms of clinical applicability over other genome editing technologies such as zinc-finger nucleases and transcription activator-like effector nucleases because of easy in vivo delivery. Here, we review and discuss the applicability of CRISPR/Cas9 to preclinical studies or gene therapy in hereditary movement disorders.
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PMID:Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders. 2766 85